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Projects

Biased incretin receptor signaling to improve metabolic efficacy

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Co-agonists at the receptors for glucagon-like peptide-1 and glucose-dependent insulinotropic polypep-tide are in clinical trials for the treatment of obesity and diabetes.

Non-canonical control of Gαi3 by Girdin and Gpsm1 in autophagy

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Autophagy represents an essential cellular survival mechanism that eliminates cellular components through lysosome-mediated degradation to main-tain cellular and orga-nismic homeostasis.

Targeting the non-canonical G protein signaling via Girdin inhibition:
from ligand to tracer development

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Girdin (GIV) is a key activator of Gi pro-teins that links RTK and GPCR signaling to PI3K-Akt activation and reduced cAMP levels, driving pro-cesses like cell migration and meta-stasis; its overexpres-

sion in cancers makes it a promising therapeutic target, and the recently discovered selective inhibitor IGGi-11 offers the first proof-of-concept for pharmacologically blocking Girdin-mediated tumor progression.

Dissecting non-canonical from canonical Gαi-dependent pathways in ischemia- reperfusion injury

Cardiovascular diseases and stroke belong to the leading cau-ses of death worldwide.

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After ischemia, the subsequent reperfu​fusion process promotes a local inflammation mediated by infiltrating neutrophils and ROS, exacerbating tissue damage and leading to reperfusion injury. G protein signal transduction modulates cell recruitment into inflammatory tissue, however Gi-driven canonical vs. non-canonical contribution is still elusive. 

Role of nucleoside diphosphate kinases in primary tumors and metastases of renal cell carcinoma

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Members of the non-mitochondrial nucleoside diphosphate kinase (NDPK) class I isoforms lead to the non-canonical activation of G proteins that serve as proto-oncogenes in renal cell carcinoma.

Role for Girdin and Daple in melanoma progression and therapy resistance

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Proposed role of Girdin and Daple in melanoma progression and therapy resistance and crosstalk with other activated signaling pathways in melanoma. 

Mode of action of the Gαi/ Gpsm2 and the RGS4 / neurabin complex in cochlear hair cells

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During the development of the inner ear, Gai3 and its non-canonical regulator Gpsm2 play an essential role for orienting sensory hair cells. In addition, in the mature organ of Corti, Gai3 signalling is involved in protective mechanisms during noise trauma.

Modulation of heterotrimeric
G protein activity by nucleoside diphosphate kinase

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Nucleoside diphosphate kinases (NDPKs) form complexes with heterotrimeric G proteins and provide GTP for the activation of these signal transducers. Thus, their function as activator of G protein signaling (AGS) is investigated in this project.

Platelet-derived stimulators of non-canonical neutrophil GPCR signaling in NETosis and thrombosis

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Thrombo-occlusive disorders such as acute myocardial infarction, ischemic stroke and venous thromboembolism are still the leading cause for morbidity and mortality worldwide. The development and progression of these disorders is driven by a complex interplay of platelets and immune cells such as particularly neutrophils.

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